[Uveitis in multiple sclerosis : Overview and perspectives]. / Uveitis bei multipler Sklerose : Übersicht und Ausblick.

The association of uveitis and multiple sclerosis (MS) is less well known than the association between optic neuritis and MS even though MS patients suffer ten times more often from uveitis than the normal population. In this group of patients, intermediate uveitis presenting with periphlebitis and "snowbanks" or "snowballs", as well as granulomatous anterior uveitis play an important role. Simultaneous occurrence of MS and uveitis could be due to the fact that both neural and ocular tissues have the same embryological origin or could be the consequence of an immunological reaction following an Epstein-Barr virus infection. The aim is to find a drug for these patients that treats both MS and uveitis. Currently various studies with different drugs already used successfully in MS patients are under investigation for use in the treatment of uveitis. There is some evidence that interferon beta is effective in macular edema associated with uveitis. Other substances, such as daclizumab, natalizumab and fingolimod also seem to be promising.

Three years of experience with QuantiFERON-TB gold testing in patients with uveitis.

PURPOSE: Overview of the results of QuantiFERON-TB Gold (QFT) testing on uveitis patients in an interdisciplinary setting for a period of 3 years. METHODS: Database search of all the patients tested for tuberculosis (Tb) with QFT. RESULTS: Of 343 tested patients, overall 80 (23.3%) were positive and 253 (73.8%) negative (results were nonconclusive for 10 patients). Anatomic localization of the patients who tested positive were distributed (% of QFT(+) tests) as anterior n = 12 (15.0%), intermediate n = 22 (27.5%), posterior n = 26 (32.5%), and pan n = 18 (22.5%). In 43 QFT(+) patients we presumed a diagnosis of Tb due to additional clinical findings. Of these patients 16 were treated with full therapy following WHO recommendations. CONCLUSIONS: QFT testing gives surprisingly high numbers of positives in uveitis patients. This is not sufficiently explained by immigrant status of the patients. The frequency of positives is substantially higher than in other cohorts. This raises important questions regarding treatment implications.

[Management of patients with ocular diseases during pregnancy. Diabetes, glaucoma and uveitis]. / Führung von Patientinnen mit Augenerkrankungen während der Schwangerschaft. Diabetes, Glaukom, Uveitis.

Many ocular diseases require treatment even during pregnancy. Some conditions, such as diabetic retinopathy tend to worsen during pregnancy but others, such as uveitis may benefit from the physiological changes occurring during pregnancy. But generally even a favorable development is not sufficient to obtain a steady state without treatment. Each medication applied during pregnancy should only be given after thorough consideration of the pros and cons and discussion of these with the patient. There are sufficient medications for ocular diseases that can be given when indicated following published guidelines and experiences. This review focuses on the course and therapy of glaucoma, diabetic retinopathy and uveitis during pregnancy.

Evidence-based, interdisciplinary guidelines for anti-inflammatory treatment of uveitis associated with juvenile idiopathic arthritis.

Uveitis in juvenile idiopathic arthritis (JIA) is frequently associated with the development of complications and visual loss. Topical corticosteroids are the first-choice therapy, and immunosuppression is commonly used. However, treatment has not been standardized. Representatives from the German Ophthalmological Society, Society for Childhood and Adolescent Rheumatology, and the German Society for Rheumatology reached consensus on a standardized treatment strategy according to disease severity in the individual patient. The recommendations were based on a systematic literature analysis in MEDLINE and consensus expert meetings. Evidence and recommendations were graded, and an algorithm for anti-inflammatory treatment and final statements confirmed in a Delphi method. An interdisciplinary, evidence-based treatment guideline for JIA uveitis is presented.

[Therapy for childhood uveitis: biologics: too often--too late?]. / Uveitistherapie im Kindesalter: Biologika: zu oft--zu spät?

Pediatric uveitis differs from uveitis seen in adulthood not only because of the uveitis presentation and severity of disease but also by a worse prognosis and age-specific problems that may occur under therapy. Biologics are selective acting proteins that are manufactured by biotechnology. The greatest amount of knowledge to date exists for the TNF alpha blocking agents. Experimental and clinical studies showed that TNF alpha plays a significant role in the process of intraocular inflammation, so it was a logical step to use TNF blocking agents in uveitis therapy. Randomized controlled studies are rare, but pooled data (as presented here) of case series published show good evidence for the efficacy especially of infliximab and adalimumab. It is to be hoped that blindness and severe sight disabilities can be further reduced by this treatment in the future. From pediatric rheumatology we have learned about even newer biologics. With this review we want to show the weaknesses and strengths of therapy with biologics and want to help in choosing this treatment at the indicated time point in the disease.

HLA-DRB1*0102 is associated with TINU syndrome and bilateral, sudden-onset anterior uveitis but not with interstitial nephritis alone.

BACKGROUND: Tubulointerstitial nephritis and uveitis (TINU) syndrome is a rare form of uveitis. Previously, the authors had demonstrated a strong association of human leukocyte antigen (HLA) DRB1*0102 with TINU. Here, the authors performed HLA analysis on subjects with isolated bilateral sudden-onset uveitis (as in the TINU subtype) or with isolated tubulointerstitial nephritis (TIN). METHODS: Patients with sudden onset, anterior, bilateral uveitis not fulfilling a diagnosis of TINU were identified. Pathology reports were reviewed to identify subjects with biopsy-proven TIN. Molecular typing of the HLA-DRB1 gene was performed by the Luminex technology-based sequence-specific oligonucleotide (SSO) hybridisation method (One Lambda, Canoga Park, California). HLA-DRB1 allele frequencies were compared with normal published controls (http://www.ncbi.nlm.nih.gov/projects/gv/mhc/ihwg.cgi dbMHC Europe cohort) and the published TINU cohort (n=18). RESULTS: The authors included 28 subjects with uveitis and 14 with TIN. There was a significantly higher frequency of DRB1*0102 in the isolated uveitis cohort versus in normal controls (10.7% vs 0.6%, respectively, p<0.0001; RR 14.3 (6.9-29.8)). None of the nephritis patients showed this HLA subtype. Another association with HLA-DRB1*08 was seen in the isolated uveitis cohort with an allele frequency of 10.7% versus 2.7% in normal controls (p=0.0019; RR 4.0 (1.8-9.0)). In contrast, the HLA-DRB1*08 was not different from controls in the TINU cohort (allele frequency 2.8%, p=not significant). CONCLUSION: The incidence of HLA-DRB1*0102 is increased in sudden-onset bilateral anterior uveitis, as seen in patients with TINU. The same allele does not appear to occur in increased frequency in patients with isolated TIN. HLA DRB1*0102 might predispose to this subset of uveitis.

[Anti-TNF-α treatment for uveitis. Analysis of the current situation]. / Anti-TNF-Therapie bei Uveitis. Eine Standortbestimmung.

Biologicals are selectively acting proteins that demonstrated high efficacy in the treatment of chronic disorders. In particular, biologicals blocking tumor necrosis factor α (TNF-α), an essential cytokine in chronic inflammatory diseases, have demonstrated great promise. Experimental and clinical data indicate that TNF-α plays an important role in intraocular inflammation. Neutralization of TNF-α might therefore be a promising strategy for prevention and treatment of uveitis. Here we review the principle effects, therapeutic value, and potential side effects of anti-TNF agents in uveitis.

[Ocular involvement in spondyloarthropathies: HLA B27 associated uveitis]. / Augenbeteiligung bei Spondyloarthritiden: HLA-B27-assoziierte Uveitis.

The most frequent extraarticular manifestation in spondyloarthropathies (SpA) is eye involvement, which is found in 30%-50% of patients. HLA B27 positive patients in particular--mostly those in the subgroup with ankylosing spondylitis--are affected. Prevalence of uveitis increases with duration of disease. Typical eye involvement is sudden-onset unilateral anterior uveitis (iridocyclitis). Most cases respond well to topical corticosteroids. Frequently relapsing or chronic cases may require oral corticosteroids in addition to classical immunosuppressive drugs and, to an increasing extent, also TNF-alpha inhibitors. In the case of the latter, monoclonal antibodies are preferred over receptor antagonists. Acute anterior uveitis may occur as a minimal variation or initial symptom of SpA. These patients should also be seen by a rheumatologist since undiagnosed SpA may be present in a significant percentage and should be included in therapeutic considerations.

Endotoxin upregulates CCR7 and its ligands in the lymphatic-free mouse iris.

PURPOSE: Using time lapse intravital microscopy and histology, we previously reported that we could not detect migration of antigen-presenting cells from the iris to the regional lymph node. Dendritic cells (DC) in other peripheral tissues migrate to lymph nodes in response to chemokines, CCL19 (ELC) and CCL21b (SLC), that activate the CCR7 receptor. We hypothesized that DCs in an inflamed iris might show a different chemokine receptor and ligand profile, thus explaining the DC's inability to migrate. METHODS: Eyes of 35 BALB/c mice were injected intravitreally with 2 mul of 250 ng E. coli lipopolysaccharide (LPS) or phosphate buffered saline (PBS). Five mice served as naïve controls. After 3 and 6 h, the iris-ciliary bodies were dissected and pooled in groups of five. Total RNA was isolated, and reverse-transcriptase polymerase chain reaction (RT-PCR) for chemokine receptor and ligand mRNA was performed. In addition, one eye from each of the three animals was taken 6 h after LPS injection for immunohistology (IHC). RESULTS: The naïve iris, the iris after PBS injection, and the iris after LPS injection contained CCR5 mRNA at approximately equal levels and did not have detectable CCR6 mRNA. No CCR7 mRNA expression was found in the naïve iris, but it was weakly expressed in PBS-injected eyes and was approximately 3.4 fold upregulated after LPS injection. This was confirmed by IHC with no staining for CCR7 in the control iris but positive staining in the inflamed eyes. Transcripts for the CCR7 ligands, CCL19 and CCL21b, were found after LPS or PBS injection but not in naïve iris-ciliary bodies. CONCLUSIONS: The clear upregulation of CCR7 and its ligands in the inflamed iris suggests that another mechanism prevents iris DCs from migrating. Other possibilities include the absence of co-factors, inhibitory substances, the lack of lymphatics inside the eye, or inadequate biologicAL activity of these chemotactic factors and ligands.

[Treatment of acute postoperative endophthalmitis. New aspects in an emergency situation]. / Therapie der akuten postoperativen endophthalmitis : Aktuelle aspekte in der behandlung eines medizinischen notfalls.

Endophthalmitis is an emergency situation. The diagnosis is based on clinical suspicion. Changing age demographics in industrialized populations and increasing numbers of cataract surgeries as well as intravitreal injections in patients with age-related macular degeneration are resulting in increasing numbers of cases of postoperative endophthalmitis. Prevention and adequate treatment considering new data from the recently published study by the European Society of Cataract and Refractive Surgeons (ESCRS) are important factors for rehabilitation. This review summarizes ESCRS data on risk factors, surgical techniques, and therapeutic options. An early, complete vitrectomy with irrigation of the anterior chamber and capsular bag is recommended.

[Inhibitors of tumour necrosis factor-alpha for the treatment of arthritis and uveitis in childhood]. / Die Inhibitoren von Tumor Nekrose Faktor alpha zur Behandlung von Arthritis und Uveitis im Kindesalter.

BACKGROUND: Chronic uveitis in childhood is a common complication of juvenile idiopathic arthritis (JIA) that frequently leads to loss of vision. Besides from corticosteroids and immunosuppressive drugs, Tumour necrosis factor-alpha (TNF-alpha) inhibitors are used frequently. MATERIALS AND METHODS: The literature published before September 2006 was evaluated for the usefulness of TNF-alpha inhibitors (etanercept, infliximab, adalimumab) for the treatment of JIA-associated uveitis. RESULTS: TNF-alpha inhibitors are effective drugs for the treatment of chronic uveitis in childhood. The response rate of uveitis in childhood to etanercept was approximately 50%. However, disease recurrence, first manifestations of uveitis and new complications occurred during the treatment. Infliximab and adalimumab appear to be more effective for the treatment of uveitis in childhood than etanercept. CONCLUSIONS: The therapy with TNF-alpha inhibitors is expensive and increases the long-term risk for secondary diseases, such as tuberculosis and probably malignant lymphoma. Their use should be restricted to uveitis patients not responding to corticosteroids and at least one of established immunosuppressive drugs.